Targeting neurokinin-1 receptor-expressing neurons with [Sar9,Met(O2)11 substance P-saporin

Neurosci Lett. 1999 Dec 17;277(1):1-4. doi: 10.1016/s0304-3940(99)00846-0.

Abstract

Neurons expressing neurokinin-1 receptors (NK-1R) are selectively destroyed by substance P (SP) coupled to the ribosome inactivating protein, saporin. SP-saporin produces incomplete lesions of striatal NK-1R-expressing neurons even at doses that produce non-specific damage. In the present study, we sought to determine if the more stable, NK-1R-specific SP analog conjugated to saporin, [Sar9,Met(O2)11]-SP (SSP-saporin), would selectively destroy cells expressing NK-1R, in vitro and in vivo. The results show that SSP-saporin is highly effective and selective, producing extensive ablation of striatal NK-1R expressing interneurons at doses that do not cause loss of other striatal neurons suggesting advantages over SP-saporin as a selective lesioning agent. SSP-saporin will be useful in larger species and for intraparenchymal injections.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Immunotoxins*
  • Male
  • N-Glycosyl Hydrolases*
  • Neostriatum / cytology
  • Neostriatum / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Plant Proteins / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neurokinin-1 / drug effects*
  • Receptors, Neurokinin-1 / metabolism*
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Substance P / analogs & derivatives*
  • Substance P / toxicity

Substances

  • Antineoplastic Agents, Phytogenic
  • Immunotoxins
  • Plant Proteins
  • Receptors, Neurokinin-1
  • Ribosome Inactivating Proteins, Type 1
  • substance P, Sar(9)-Met(O2)(11)-
  • Substance P
  • N-Glycosyl Hydrolases
  • Saporins